Molecular Characterization of a Somatically Mutated Anti-DNA Antibody Bearing Two Systemic Lupus Erythematosus-related Idiotypes

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1990 May 1

PMID 2110188

Citations 18

Authors

A Davidson

C Aranow

R Peterson

N Hannigan

B Diamond

Affiliations

Soon will be listed here.

Abstract

We report the molecular characterization of 2A4, an IgG, DNA-binding antibody bearing the 3I and F4 idiotypes which are associated with anti-DNA antibodies in serum of patients with systemic lupus erythematosus (SLE). The antibody is produced by an EBV-transformed B cell line derived from a patient with multiple myeloma whose myeloma protein is also an IgG, 3I-reactive, F4-reactive, DNA-binding immunoglobulin, although the 2A4 antibody does not itself represent the myeloma protein. The 2A4 heavy chain is encoded by a VH4 gene, a D-D gene fusion and the JH6 gene; the light chain is derived from a Vk1 gene and the Jk2 gene. This is the first human antibody shown to have a CDR3 encoded by a D-D fusion. DNA sequence analysis of the 2A4 VH gene together with a Southern blot of genomic DNA probed with a 2A4 VH-specific oligonucleotide strongly suggest it to be somatically mutated. The data provide evidence that human autoantibodies can be products of somatically mutated genes and suggest that the 2A4 antibody may reflect the selective pressure of antigen.

Citing Articles

Mechanisms of B cell autoimmunity in SLE.

Dorner T, Giesecke C, Lipsky P Arthritis Res Ther. 2011; 13(5):243.

PMID: 22078750 PMC: 3308063. DOI: 10.1186/ar3433.

Autoreactive T cells in murine lupus: origins and roles in autoantibody production.

Craft J, Peng S, Fujii T, Okada M, Fatenejad S Immunol Res. 1999; 19(2-3):245-57.

PMID: 10493178 DOI: 10.1007/BF02786492.

Anti-DNA antibodies as early predictor for disease exacerbations in SLE. Guideline for treatment?.

Spronk P, Bootsma H, Kallenberg C Clin Rev Allergy Immunol. 1998; 16(3):211-8.

PMID: 9773248 DOI: 10.1007/BF02737631.

VH usage and somatic hypermutation in peripheral blood B cells of patients with rheumatoid arthritis (RA).

Huang S, Jiang R, Hufnagle W, Furst D, WILSKE K, Milner E Clin Exp Immunol. 1998; 112(3):516-27.

PMID: 9649224 PMC: 1904985. DOI: 10.1046/j.1365-2249.1998.00580.x.

Lupus-specific antibodies reveal an altered pattern of somatic mutation.

Zandman-Goddard G, Davidson A, Aranow C, Diamond B J Clin Invest. 1997; 100(10):2538-46.

PMID: 9366568 PMC: 508454. DOI: 10.1172/JCI119796.

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